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Study · In vitro (cells) · 2023

2 results

Versatile Click Linker Enabling Native Peptide Release from Nanocarriers upon Redox Trigger.

Hebels ER, Dietl S, Timmers M, Hak J, van den Dikkenberg A, Rijcken CJF, Hennink WE, Liskamp RMJ, Vermonden T

Bioconjugate chemistry11 Dec 2023Cited by 7 (Europe PMC)

PMID38079189 (opens in a new tab)PMCIDPMC10739580 (opens in a new tab)DOI10.1021/acs.bioconjchem.3c00484 (opens in a new tab)PepBankPUB-38079189
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Summary

Nanocarriers have shown their ability to extend the circulation time of drugs, enhance tumor uptake, and tune drug release. Therapeutic peptides are a class of drug compounds in which nanocarrier-mediated delivery can potentially improve their therapeutic index. To this end, there is an urgent need for orthogonal covalent linker chemistry facilitating the straightforward on-the-resin peptide generation, nanocarrier conjugation, as well as the triggered release of the peptide in its native state. Here, we present a copper-free clickable ring-strained alkyne linker conjugated to the N-terminus of oncolytic peptide LTX-315 via standard solid-phase peptide synthesis (SPPS). The linker contains (1) a recently developed seven-membered ring-strained alkyne, 3,3,6,6-tetramethylthiacycloheptyne sulfoximine (TMTHSI), (2) a disulfide bond, which is sensitive to the reducing cytosolic and tumor environment, and (3) a thiobenzyl carbamate spacer enabling release of the native peptide upon cleavage of the disulfide via 1,6-elimination. We demonstrate convenient "clicking" of the hydrophilic linker-peptide conjugate to preformed pegylated core-cross-linked polymeric micelles (CCPMs) of 50 nm containing azides in the hydrophobic core under aqueous conditions at room temperature resulting in a loading capacity of 8 mass % of peptide to polymer (56% loading efficiency). This entrapment of hydrophilic cargo into/to a cross-linked hydrophobic core is a new and counterintuitive approach for this class of nanocarriers. The release of LTX-315 from the CCPMs was investigated in vitro and rapid release upon exposure to glutathione (within minutes) followed by slower 1,6-elimination (within an hour) resulted in the formation of the native peptide. Finally, cytotoxicity of LTX CCPMs as well as uptake of sulfocyanine 5-loaded CCPMs was investigated by cell culture, demonstrating successful tumor cell killing at concentrations similar to that of the free peptide treatment.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

1 result from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Efficacy outcome

    In cell culture, LTX CCPMs killed tumor cells at concentrations similar to free peptide treatment.

    In plain wordsIn cells, LTX‑315 nanocarriers killed tumor cells at concentrations similar to free peptide treatment.

    Peptide
    LTX-315
    Outcome
    Direction not reportedTumor cell killing
    Study

    n: not reported in source

    Comparator
    Free peptide treatment
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Finally, cytotoxicity of LTX CCPMs as well as uptake of sulfocyanine 5-loaded CCPMs was investigated by cell culture, demonstrating successful tumor cell killing at concentrations similar to that of the free peptide treatment.

Studies that did not test the peptide alone1

In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking LTX-315.

  1. 02LabNot a test of LTX-315 aloneIn vitro (cell-free)Pharmacokinetics

    In vitro, LTX‑315 nanocarriers released native peptide after glutathione exposure and subsequent elimination.

    In plain wordsIn lab tests, the nanocarriers released native LTX‑315 after exposure to glutathione.

    Peptide
    LTX-315
    Outcome
    Direction not reportedNative peptide release
    Study

    n: not reported in source

    Outcome group
    Pharmacokinetics · Cancer

    Source sentences

    Summary
    The release of LTX-315 from the CCPMs was investigated in vitro and rapid release upon exposure to glutathione (within minutes) followed by slower 1,6-elimination (within an hour) resulted in the formation of the native peptide.

    In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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